Commercial motor vehicle (CMV) drivers, particularly drivers of large trucks continue to be a population of concern regarding traffic safety despite the reduction in large truck crash rates over the past decade. Medication and drug use while driving is one important risk factor for large truck crashes. Work-related exposures, such as vibration, manual handling and poor ergonomics contribute to an increased risk for injuries and chronic conditions and are common reasons for opioid analgesic (OA) use by CMV truck drivers. The objectives of this study were to examine the role of OA use in CMV truck drivers involved in fatal crashes by: (a) generating prevalence estimates of OA use; (b) documenting the relationship between OA use and crash responsibility.